Human skin is composed of two major layers, the epidermis and the dermis. Below these layers lies the hypodermis, which is not usually classified as a layer of skin. The thinner outer layer of the skin, the epidermis, provides a barrier to the external environment. The epidermis is typically about 0.05 to 1.5 mm thick (varying from its minimum at the eyelids to its maximum over the palms and soles of the feet). It is composed of many different cell types including keratinocytes, melanocytes, and Langerhan cells. Keratinocytes are the major cell type (being about 75 to 80% of the total number of cells), and are responsible for keeping water in the body and keeping other harmful chemicals and pathogens out. The epidermis is made up of a stratified squamous epithelium with an underlying basement membrane. It contains no blood vessels, and is nourished by diffusion from the dermis.
The thicker inner layer of the skin, the dermis, is the major component of human skin. The dermis, or corium, is typically about 0.3 to 5 mm thick (varying from its minimum at the eyelids to its maximum over the back). It is composed of a network of connective tissue, which provides strength, elasticity, and thickness to the skin, and contains other structures including capillaries, nerve endings, hair follicles, smooth muscle, glands, and lymphatic tissue. The main cell type of the dermis is the fibroblast, which is responsible for the synthesis and secretion of dermal matrix components such as collagen, elastin, and glycosaminoglycans. Collagen provides the strength, elastin the elasticity, and glycosaminoglycans the moistness and plumpness of the skin. With ageing, the thickness of the dermal layer is reduced, and this is believed to be partially responsible for the formation of wrinkles in ageing skin.
The hypodermis, also commonly referred to as the subcutaneous fat layer or subcutaneous tissue, lies below the dermis. Its purpose is to attach the skin to underlying bone and muscle as well as to supply the dermis with blood vessels and nerves. It is made up of loose connective tissue and elastin. The main cell types are fibroblasts, macrophages, and adipocytes. The hypodermis contains about 50% of total body fat, the fat serving as padding, insulation, and an energy reserve for the body.
Facial aging occurs as the result of several factors: inherent changes within the skin, the effects of gravity, the effects of facial muscles acting on the skin (dynamic lines), soft tissue loss or shift, bone loss, and a gradual loss of tissue elasticity. The epidermis begins to thin, causing the junction with the dermis to flatten. Collagen also decreases, and bundles of collagen, which give the skin turgor, become looser and lose strength. When the skin loses elasticity it is less able to resist stretching. The skin begins to wrinkle as a result of gravity, muscle pull, and tissue changes. Water loss and a breakdown of the connective bonds between cells also weakens the barrier function of the skin, which can cause the skin's pore size to increase.
As a person ages, the face loses volume, soft tissue, and fat. The appearance of jowls and folds is usually caused by the drooping of facial tissues and the folding of skin over areas where it is attached to and supported by the muscles below. Due to the reduction in soft tissue, the face appears more hollow. In various facial areas such as the forehead, eyes, nose, midface, and lower face, changes relating to aging have been well documented. For example, in the forehead area, the forehead and brow droop over time, which lowers the eyebrows and causes the upper eyelid skin to bunch. Forehead lines appear when one tries to hold the brows and eyelids up to counteract these changes. It is well known that the eye area is often the first facial feature to show signs of aging. Skin changes around the eyes occur earlier than in the rest of the face since the skin is thinnest here. The skin in this area also contains fewer glands and is subjected to constant blinking, squinting, rubbing, and pulling.
The midface area ages when the cheeks begin to droop, causing nasolabial folds, which are the lines that run from the sides of the nose to the corners of the mouth. It is known to treat these folds with facial fillers. In the nose area, the nose appears to elongate. Common causes of elongation are thinning of the soft tissue and loss of elasticity, which causes “drooping of the tip” and unmasking of the bone, creating a new hump.
In the lower face area, facial tissues descend, causing so-called “laugh lines.” It is known to treat these folds and lines with facial fillers. Further down on the lower face, the corners of the mouth may droop, and a descent of the jowls can create folds often referred to as “marionette lines.” Furthermore, jowls form when the cheeks sag around a fixed point along the jaw where the facial muscles attach to the jawbone.
Various injectables have been used for restoring tissue loss in the face. Since the 1980s, injectable collagen has been used as a soft-tissue filler to fill wrinkles, lines, and scars on the face. Collagen is a naturally occurring protein that supports various parts of the body including skin, tendons, and ligaments. Fat injections have also been used to add volume, fill wrinkles and lines, and enhance the lips. Fat injections involve taking fat from one part of a patient's body (typically the abdomen, thighs, or buttocks) and reinjecting it beneath the facial skin. Botulinum toxins, which were first approved for the treatment of neck spasms, cranial nerve disorders, and eye spasms, have also been used “off-label” for cosmetic purposes. With the recent FDA approval of Botox for cosmetic use in the glabellar region, the drug is becoming widely used for the temporary treatment of dynamic lines. In contrast to fillers, the botulinum toxin is injected into facial muscles, temporarily blocking nerve impulses and relaxing the muscles to smooth so-called “worry lines.”
Hyaluronic acid is one of most commonly used cosmetic dermal fillers. Hyaluronic acid is a linear polysaccharide that exists naturally in all living organisms, and is a universal component of the extra-cellular spaces of body tissues. The identical structure of hyaluronic acid in all species and tissues makes this polysaccharide an ideal substance for use as a bio-material in health and medicine. Hyaluronic acid is present in many places in the human body. It gives volume to the skin, shape to the eyes, and elasticity to the joints. The highest concentrations of hyaluronic acid are found in connective tissues, and most of the hyaluronic acid produced by the human body (about 56%) is found in the skin.
Various forms of hyaluronic acid are provided commercially by a number of manufacturers. The most commonly used hyaluronic acid is a non-animal stabilized hyaluronic acid (NASHA), distributed in a clear gel form and produced by bacterial fermentation using streptococci bacteria. Different from animal-derived hyaluronic acid, the non-animal-derived hyaluronic acid is free from animal proteins. This limits the risk of animal-based disease transmission or the development of an allergic response. The most known non-animal stabilized hyaluronic acid is manufactured by Q-med AB of Seminariegatan, Uppsala, Sweden and commercially available under the tradename Restylane®. Since its commercialization in 1996, it is estimated that over 2,500,000 treatments have been carried out worldwide. Other non-animal stabilized hyaluronic acid products include Perlane® from Q-med, which has larger particles than Restylane®, and Captique™ from Genzyme Corporation. Another commonly used filler is a hyaluronic acid derivative manufactured by Genzyme Corporation and commercially available under the tradename Hylaform Plus. Hylaform Plus is a sterile, nonpyrogenic, viscoelastic, clear, colorless, transparent gel implant composed of cross-linked molecules of hyaluronan. Although hyaluronic acid and its derivatives are the most commonly used dermal fillers, they have limited long-term viability. The material must be reinjected periodically, typically every 4 to 12 months, due to hyaluronan metabolism in the body.
To increase the longevity of dermal fillers, high molecular weight formulations are being developed. However, increasing molecular weights result in higher and higher viscosities. The higher the viscosity, the more difficult it is to inject the desired amount of dermal filler into the desired location, or to extract any excess. In addition, because the dermal filler must be injected within the existing skin layers, and there is minimal ability to create a pocket for the filler to reside in, it is difficult to manipulate high molecular weight fillers within existing skin tissue to achieve the desired cosmetic effect. Also, once injected, high molecular weight dermal fillers may shift to a different location and create an undesirable cosmetic defect. Current methods which seek to use a lysing agent to remove excess or unwanted filler do not provide much differential action with respect to native tissue, causing damage to adjacent tissues and substantially increasing the risk of a poor aesthetic outcome.
Ultrasonic energy can be used to shear-thin highly viscous materials, and the applicants have found that ultrasonic energy can successfully be used to shear-thin collagen-based dermal fillers. The energy can be applied via direct contact ultrasound (at frequencies of 20-200 kHz) or via high intensity, focused, field effect ultrasound or “HIFU” (at frequencies of 50 kHz-20 MHz). Since a non-thermal shearing action will be desired from the HIFU source, the frequencies of interest will dip below the traditional lower frequency limit of high frequency medical ultrasound, 500 kHz, to at least 100 kHz. The lower frequency limit will typically be defined by the desired resolution of the focal point for treatment. Ultrasonic energy can also be used to undermine or dissect tissue, to release folds, or to create pockets within tissue.
The requirements and construction of devices for delivering contact ultrasound and HIFU will be different. Contact devices must come into direct contact with a filler in order for an ultrasonic element to shear-thin the filler material. HIFU devices, on the other hand, focus field effect ultrasound so as to shear-thin the filler material without direct contact between the ultrasound radiator and the filler. However, readily known devices are deficient in that contact devices are generally designed for the macroscopic coagulation or ablation of tissue surfaces, while HIFU devices are generally designed for the image-guided hyperthermic, coagulative, or cavitation-induced destruction of tissue at depth. Accordingly, improved ultrasonic apparatuses that are safe and effective for non-thermal, shallow depth dermatological treatments are required. In addition, methods for manipulating high molecular weight, high viscosity dermal fillers and shallow facial tissues are desired.